In order to study the function of the nonmuscle myosin II isoforms (NMII-A, II-B, and II-C), homologous recombination has been used to delete each isoform in embryonic stem cells and null mice have been generated. Deletion of nonmuscle myosin heavy chain (NMHC) II-A causes lethality prior to gastrulation (E6.5) and the embryos are disorganized with defects in cell-cell adhesion and a failure to form a columnar visceral endoderm. In order to avoid the early embryonic lethality, a NMHC II-A floxed mouse has been created. A neomycin-resistance cassette has been inserted into the intron prior to exon 3 and loxP sites have been inserted flanking both the neomycin cassette and the exon. Matings of these mice to mice bearing cre recombinase under the control of a cell or tissue specific promoters causes the corresponding deletion of NM II-A. It is known that humans with mutations in MYH9 have defects in bleeding times, hearing loss, cataracts, and glomerular nephritis. Because of the severity of the kidney disorder, initial studies focus on deletion of NM II-A in kidney podocytes which are the kidney cells which form part of the filtration barrier in the glomerulus. Effacement of podocytes is seen in kidney biopsies from MYH9RD patients. Since it is currently not clear whether the disease results from interference of the mutant myosin with the wild type NMIIA or from haploinsufficiency these deletions may provide important information about the role of NMIIA in podocyte function. The NM II-A mice have been crossed to mice with cre recombinase controlled by the podocyte marker, podocin which has been successfully used to generate podocyte-specific deletions. Homozygous mice for deletion of NMIIA (Apod/Apod) have increased concentrations of albumin in urine samples by 6 months of age indicating a decrease in glomerular filtration.